On Feb. 22, the U.S. Food and Drug Administration (FDA) hosted a webinar, as it noted, “for stakeholders interested in learning more about the draft guidances on COVID-19 transition plans for medical devices.”
It was most certainly a valuable use of 90 minutes. At the same time, it no doubt raised myriad questions for drug manufacturers and medical device companies seeking to gain a better understanding of their legal and manufacturing obligations after they had gained emergency use authorization (EUA) in response to the COVID-19 Public Health Emergency (PHE).
As drug and medical device makers are confronted with transitioning back to full regulatory compliance under a proposed three-phase plan (detailed below), they would be well served to understand the history and purpose of the EUA, learn about the ongoing challenges and benefits of its use, and follow a new process in the wake of EUA approval in a post-pandemic environment.
The EUA: Nearly two decades in use
While many may associate the EUA as a new term that cropped up in response to the pandemic, the reality is quite different. The EUA program was established in 2004 when the Project BioShield Act was signed into law, amending Section 564 of the Federal Food, Drug, and Cosmetic Act. Under Section 564, “the FDA may authorize unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening disease.
According to published accounts, the law gave private companies $5.6 billion in incentives to develop antidotes to biological and chemical weapons.
The bill was signed nearly three years after the terrorist attacks on the United States on Sept. 11, 2001, when many Americans and lawmakers saw their lives disrupted by potential biological threats. In a story in The New York Times on July 15, 2004, President George W. Bush said the new bill would “break new ground in the search for treatments and cures while strengthening our overall biotechnology infrastructure.”
The last sentence of the story served as a telling statement given today’s world. “The bill also accelerates the approval process for vaccines and, in an emergency, let the government distribute certain treatments before the Food and Drug Administration approves them.”
With this serving as the backdrop, the FDA says the EUA “is a mechanism to facilitate the availability and use of medical countermeasures, including vaccines, during public health emergencies, such as the current COVID-19 pandemic.”
The passage continues: “Under an EUA, FDA may allow the use of unapproved medical products, or unapproved uses of approved medical products in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions when certain statutory criteria have been met, including that there are no adequate, approved, and available alternatives. Taking into consideration input from the FDA, manufacturers decide whether and when to submit an EUA request to FDA.”
Managing challenges, aiming for gains
There have been considerable challenges with EUAs during the pandemic. An article on the University of Minnesota’s Center for Infectious Disease Research and Policy website, citing a story in JAMA Internal Medicine in December, said that most EUAs for COVID-19–related medical products “…were not supported by high-quality data, and the FDA revoked authorizations for products because of effectiveness or safety problems.”
Similarly, the Minnesota research group said that the researchers from Tel Aviv University studied COVID-19–related EUAs issued from Jan. 1, 2020, to Jan. 22, 2021, on the FDA website “and categorized them by their trial designs. The team ascertained product EUA status on Oct 1, 2021.”
“Among the 393 COVID-19–related medical products given EUAs, 329 (84%) were diagnostic tests, 54 (14%) were medical devices, and 10 (3%) were drugs or vaccines,” read the article.
In the research letter written in JAMA, the Tel Aviv researchers wrote that “Most medical devices were granted EUAs without any documented supporting data, and only a small number were supported by clinical data.”
The researchers were critical of the FDA. “In future public health emergencies, the FDA should consider raising the standard of evidence required for EUAs after several diagnostic products are marketed to ensure their accuracy.”
Despite the challenges, there have been clear benefits. As of this writing in mid-March, nearly 217 million Americans are fully vaccinated against COVID-19, according to the Centers for Disease Control and Prevention’s COVID Data Tracker.
That’s a positive development and was made possible by the EUAs for the Johnson & Johnson, Pfizer-BioNTech, and Moderna vaccines. Additionally, supply problems with medical devices (e.g. face masks) were alleviated by the agency's use of the EUA framework to supplement supply and innovative devices were brought to market to protect our health care professionals.
A phased approach
All of this background leads to one central question for pharmaceutical companies and medical device makers: Now that the FDA is calling for EUA-approved products to gain traditional approval, what steps do pharmaceutical companies need to take?
The FDA has issued guidance, which applies to devices that have been issued an EUA under the previously mentioned section 564 of the Federal Food, Drug and Cosmetic Act. During the webinar in February, the FDA presented slides detailing the background of EUAs, transition guidances, scope, and examples. There is a lot at stake for companies as more than 900 EUAs were issued.
The FDA’s action recommendations for the return-to-normal operations align with a 180-day, three-phased approach. The FDA offered a few examples. In one scenario, the agency provided an example of how a continuous ventilator was authorized under the umbrella EUA for ventilators.
In phase 1, or by July 1 in this example, the manufacturer’s transition implementation date would begin upon publication of advance notice of termination of the relevant EUA declaration in the Federal Register.
In phase 2, by Aug. 1, the manufacturer would submit a notification of intent to inform the FDA that it does not intend to pursue a marketing authorization.
And in phase 3, by Jan. 1, 2023, or 180 days after the implementation date—the relevant EUA declaration is terminated, and the umbrella EUA is no longer in effect. According to the FDA, the manufacturer in this scenario must cease distribution of the device. The FDA does not intend to object, however, if this manufacturer develops a plan for already distributed product to remain distributed.
The FDA provided a second example of a telethermographic system. These devices “detect infrared light emitted from a person’s skin and convert that information into a temperature map of a region of the body,” according to the JAMA Network.
In phase 1, all manufacturers of the system would continue to comply with the requirements that were not addressed in the enforcement policy, regardless of whether they intend to distribute their devices beyond the COVID-19 PHE.
In phase 2, a manufacturer that intends to distribute beyond PHE registers and submits a marketing submission while a manufacturer that does not intend to distribute beyond PHE ceases distribution during phase 2 and notifies users of the regulatory status.
In phase 3, a manufacturer that intends to distribute beyond PHE engages with the FDA to address already-distributed devices, while a manufacturer that does not intend to distribute beyond PHE makes revised labeling publicly available, sends notices to users, and continues to report adverse events.
It’s a lot to digest, but device and drug makers would do well to review and follow the FDA guidance and reach out to them with their comments about the new rules and regulations as quickly as possible.